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Amebiasis

Amebiasis is caused by Entamoeba histolytica, a protozoan found worldwide. The highest prevalence of amebiasis is in developing countries where barriers between human feces and food and water supplies are inadequate.

Although most cases of amebiasis are asymptomatic, dysentery and invasive extraintestinal disease can occur. Amebic liver abscess is the most common manifestation of invasive amebiasis, but other organs can also be involved, including pleuropulmonary, cardiac, cerebral, renal, genitourinary, and cutaneous sites. In developed countries, amebiasis primarily affects migrants from and travelers to endemic regions, men who have sex with men, and immunosuppressed or institutionalized individuals.

E histolytica is transmitted via ingestion of the cystic form (infective stage) of the protozoa. Viable in the environment for weeks to months, cysts can be found in fecally contaminated soil, fertilizer, or water or on the contaminated hands of food handlers. Fecal-oral transmission can also occur in the setting of anal sexual practices or direct rectal inoculation through colonic irrigation devices. Excystation then occurs in the terminal ileum or colon, resulting in trophozoites (invasive form). The trophozoites can penetrate and invade the colonic mucosal barrier, leading to tissue destruction, secretory bloody diarrhea, and colitis resembling inflammatory bowel disease. In addition, the trophozoites can spread hematogenously via the portal circulation to the liver or even to more distant organs.

Patophysiology

When cyst is swallowed, it passes through the stomach unharmed and shows no activity while in an acidic environment. When it reaches the alkaline medium of the intestine, the metacyst begins to move within the cyst wall, which rapidly weakens and tears. The quadrinucleate amoeba emerges and divides into amebulas that are swept down into the cecum. This is the first opportunity of the organism to colonize, and its success depends on one or more metacystic trophozoites making contact with the mucosa. Mature cyst in the large intestines leaves the host in great numbers (the host remains asymptomatic). The cyst can remain viable and infective in moist and cool environment for at least 12 days, and in water for 30 days. The cysts are resistant to levels of chlorine normally used for water purification. They are rapidly killed by purification, desiccation and temperatures below 5 and above 40 degrees.

The metacystic trophozoites of their progenies reach the cecum and those that come in contact with the oral mucosa penetrate or invade the epithelium by lytic digestion. The trophozoites burrow deeper with tendency to spread laterally or continue the lysis of cells until they reach the sub-mucosa forming flash-shape ulcers. There may be several points of penetration. From the primary site of invasion, secondary lesions maybe produced at the lower level of the large intestine. Progenies of the initial colonies are squeezed out to the lower portion of the bowel and thus, have the opportunity to invade and produce additional ulcers. Eventually, the whole colon may be involved. E. histolytica has been demonstrated in practically every soft organ of the body. Trophozoites which reach the muscularis mucosa frequently erode the lymphatics or walls of the mesenteric venules in the floor of the ulcers, and are carried to the intrahepatic portal vein.

If thrombi occur in the small branches of the portal veins, the trophozoites in thrombi cause lytic necrosis on the wall of the vessels and digest a pathway into the lobules. The colonies increase in size and develop into abscess. A typical liver abscess develops and consists of:

Central zone necrosis Median zone of stoma only An outer zone of normal tissue newly invaded by amoeba. Most amoebic abscess of the liver are in the right lobe. Next to the liver, the organ which is the frequent site of extra-intestinal amoebiasis is the lungs. This commonly develops as an extension of the hepatic abscess.

Presentation

Amebic colitis

The most common presentation of amebic colitis is gradual onset of bloody diarrhea,

abdominal pain, and tenderness spanning several weeks’ duration.

Rectal bleeding without diarrhea can occur, especially in children.

Only approximately 10-30% of patients with amebic colitis develop fever.

Weight loss and anorexia may occur.

Fulminant or necrotizing colitis usually manifests as severe bloody diarrhea and

widespread abdominal pain with evidence of peritonitis and fever. Predisposing factors for fulminant colitis include poor nutrition, pregnancy,

corticosteroid use, and very young age. Fever (10-30%)

Weight loss (40%)

Diffuse abdominal tenderness (12-85%)

Heme-positive stools (70-100%)

Abdominal pain, distension, and rebound tenderness likely in fulminant colitis

Amebic liver abscess

The most typical presentation of amebic liver abscess is fever, right upper quadrant

pain, and tenderness of less than 10 days’ duration.

 

Unlike amebic colitis, amebic liver abscess is associated with fever in 85-90% of cases.

A more subacute presentation anorexia.

can be seen, with concomitant weight loss and

Cough can occur. Jaundice is unusual.

 

Acute

abdominal

symptoms

and

signs

should

prompt rapid investigation for

intraperitoneal rupture. Sixty to 70% of patients with amebic liver abscess do not have concomitant colitis,

A history of alcohol abuse is common, but a clear causal relationship is unclear.

although a history of dysentery within the previous year may be obtained. Amebic liver abscess may manifest years after travel to or residency in an endemic

area.

Fever (85-90%)

Right upper quadrant abdominal tenderness (84-90%)

Weight loss (33-50%)

Hepatomegaly (30-50%)

Jaundice (6-10%)

Pleuropulmonary amebiasis: Cough, pleuritic chest pain, and respiratory distress may be clues to rupture through the diaphragm, a rare but serious complication of amebic liver abscess.

Cerebral amebiasis Occurring in 0.6% of amebic liver abscess cases, abrupt onset of nausea, vomiting, headache, and mental status change should prompt rapid investigation for CNS involvement. Progression can be very rapid.

Lab Studies

Microscopy Microscopic stool examination for trophozoites from a single stool sample in amebic colitis is only 33-50% sensitive. Examination of 3 stool samples over no more than 10 days can improve the detection rate to 85-95%. See the image below.

Lab Studies Microscopy  Microscopic stool examination for trophozoites from a single stool sample in amebicshigellosis . Stool examination findings in patients with amebic liver abscess are usually negative. Repeated stool sampling in patients with proven amebic liver abscess is positive in 8- 40% of cases. Identification of the parasite in a liver abscess aspirate is only 20% sensitive. The presence of intracytoplasmic red blood cells in trophozoites is diagnostic of E histolytica infection, although recent studies demonstrated the same phenomenon with E dispar .  The World Health Organization (WHO) recommends that intestinal amebiasis be diagnosed with an E histolytica -specific test, thus rendering the classic stool ova and parasite examination obsolete.   Culture Xenic cultivation, first introduced in 1925, is defined as the growth of the parasite in the presence of an undefined flora. This technique is still in use today using modified Locke-egg media.  Axenic cultivation, first achieved in 1961, involves growth of the parasite in the absence of any other metabolizing cells. Only a few strains of E dispar have been reported to be viable in axenic cultures.  Cultures can be performed using fecal or rectal biopsy specimens and liver abscess aspirates. The success rate is between 50% and 70%, but the technique is technically difficult. Overall, it is less sensitive than microscopy.  Antigen detection  Enzyme-linked immunosorbent assay (ELISA) is used to detect antigens from E histolytica in stool samples. Several kits are commercially available. Antigen-based ELISA kits using monoclonal antibodies against the GAL/GalNAc – specific lectin of E histolytica ( E histolytica II, TechLab, Blacksburg, VA) yield an overall sensitivity of 71%-100% and specificity of 93%-100%. One study showed a much lower sensitivity (14.2%). In patients with amebic liver abscess, serum and liver aspirate antigen detection using the same kit was shown to yield a sensitivity of 96% and 100%, respectively. Other stool detection kits use monoclonal antibodies against the serine-rich antigen of E histolytica (Optimum S kit, Merlin Diagniostika, Bornheim-Hersel, Germany) or against other specific antigens ( Entamoeba CELISA-PATH, Cellabs, Brookvale, Australia; ProSpecT EIA, Remle Inc, Lenexa, KY). No specific antigen tests are available for the detection of E dispar and E moshkovskii from clinical samples.     " id="pdf-obj-2-8" src="pdf-obj-2-8.jpg">

Trichrome stain of Entamoeba histolytica trophozoites in amebiasis. Two diagnostic characteristics are observed. Two trophozoites have ingested erythrocytes, and all 3 have

nuclei with small, centrally located karyosomes. Stool leukocytes may be found, but in fewer numbers than in shigellosis. Stool examination findings in patients with amebic liver abscess are usually negative. Repeated stool sampling in patients with proven amebic liver abscess is positive in 8- 40% of cases. Identification of the parasite in a liver abscess aspirate is only 20% sensitive. The presence of intracytoplasmic red blood cells in trophozoites is diagnostic of E histolytica infection, although recent studies demonstrated the same phenomenon with E dispar. The World Health Organization (WHO) recommends that intestinal amebiasis be diagnosed with an E histolytica -specific test, thus rendering the classic stool ova and parasite examination obsolete.

Culture Xenic cultivation, first introduced in 1925, is defined as the growth of the parasite in the presence of an undefined flora. This technique is still in use today using modified Locke-egg media.

Axenic cultivation, first achieved in 1961, involves growth of the parasite in the absence of any other metabolizing cells. Only a few strains of E dispar have been reported to be viable in axenic cultures. Cultures can be performed using fecal or rectal biopsy specimens and liver abscess aspirates. The success rate is between 50% and 70%, but the technique is technically difficult. Overall, it is less sensitive than microscopy.

Antigen detection Enzyme-linked immunosorbent assay (ELISA) is used to detect antigens from E histolytica in stool samples. Several kits are commercially available. Antigen-based ELISA kits using monoclonal antibodies against the GAL/GalNAcspecific lectin of E histolytica (E histolytica II, TechLab, Blacksburg, VA) yield an overall sensitivity of 71%-100% and specificity of 93%-100%. One study showed a much lower sensitivity (14.2%). In patients with amebic liver abscess, serum and liver aspirate antigen detection using the same kit was shown to yield a sensitivity of 96% and 100%, respectively. Other stool detection kits use monoclonal antibodies against the serine-rich antigen of E histolytica (Optimum S kit, Merlin Diagniostika, Bornheim-Hersel, Germany) or against other specific antigens (Entamoeba CELISA-PATH, Cellabs, Brookvale, Australia; ProSpecT EIA, Remle Inc, Lenexa, KY). No specific antigen tests are available for the detection of E dispar and E moshkovskii from clinical samples.

Serology Multiple serologic assays are available for the diagnosis of amebiasis. ELISA is the most used assay throughout the world and is used to measure the presence of serum antilectin antibodies (IgG). The sensitivity for detection of antibodies to E histolytica in patients with amebic liver abscess is 97.9%, whereas the specificity is 94.8%. False-negative results can occur within the first 7-10 days following infection. Immunofluorescent assay (IFA) is also rapid, reliable, and reproducible. In the setting of amebic liver abscess, the sensitivity and specificity of IFA was shown to be 93.6% and 96.7%, respectively.

Indirect hemagglutination (IHA) is very specific (99.1%) but is less sensitive than

Polymerase chain reaction

Nonspecific laboratory tests

ELISA. Immunoelectrophoresis, counter-immunoelectrophoresis (CIE), and immunodiffusion

tests use the precipitation property of antigen-antibody complexes in agar. CIE is time-consuming but has shown a sensitivity of 100% in invasive amebiasis. Complement fixation (CF) is less sensitive than other techniques.

The seropositivity prevalence is very high in endemic areas, limiting antibody-based

testing for diagnosing currently active disease, since antibodies can persist for years after infection.

E histolytica can be identified in various types of clinical specimens, including feces,

tissues, and liver abscess aspirates. A wide variety of polymerase chain reaction (PCR) methods targeting different genes,

including a small-subunit rRNA gene (18S rDNA), 30-kDa antigen gene, serine-rich protein gene, chitinase gene, hemolysin gene, and extrachromosomal circular DNA, have been described for the detection and differentiation of E histolytica, E dispar, and E moshkovskii. Sensitivities can vary according to sampling and the specific target gene used.

Performed on feces, PCR yields a sensitivity that is similar to that of stool antigen- based assay. PCR-based tests have been strongly endorsed by the WHO.

Application of PCR-based methods in routine diagnosis is still very limited, as the

generation of nonspecific DNA fragments from environmental and clinical samples often leads to false-positive results

Amebic liver abscess

  • Leukocytosis without eosinophilia (80%)

  • Elevated alkaline phosphatase (80%)

  • Mildly elevated transaminases

  • Mild anemia

  • Elevated erythrocyte sedimentation rate

Imaging Studies

Both ultrasonography and CT scanning are sensitive but nonspecific for amebic liver

abscess. Lesions are usually solitary and located in the right hepatic lobe (70-80%), although multiple abscesses are possible. On sonograms, amebic liver abscesses usually appear as a homogenous hypoechoic

round lesion. On CT scans with intravenous contrast, amebic liver abscess can appear as a rounded, low-attenuation lesion with an enhancing rim. Furthermore, the abscess may be homogenous or septated, with or without observable fluid levels.

Histological Findings

The intestinal biopsy specimen should be taken from the edge of ulcers and evaluated for motile trophozoites. Histopathological findings can comprise of mucosal thickening, multiple discrete ulcers

separated by regions of normal-appearing colonic mucosa, diffusely inflamed and edematous mucosa, necrosis, or wall perforation. Amebic invasion through the mucosa and into submucosal tissues is the hallmark of amebic colitis. Lateral extension through the submucosal tissues gives rise to the classic flask-shaped ulcer of amebic colitis. Different chemical stains can be used, including periodic acid-Schiff stain, which makes E histolytica appear magenta in color.

Medical Care

Most individuals with amebiasis may be treated on an outpatient basis. Several clinical scenarios may favor inpatient care, as follows:

Severe colitis and hypovolemia requiring intravenous volume replacement

Liver abscess of uncertain etiology or not responding to empirical therapy

Fulminant colitis requiring surgical evaluation

Peritonitis and suspected amebic liver abscess rupture

Surgical Care

Prompt surgical evaluation is needed in suspected cases of fulminant colitis, peritonitis, or perforated viscus.

Surgical intervention is usually indicated in different clinical scenarios: uncertain diagnosis (possibility of pyogenic liver abscess); concern of bacterial suprainfection in amebic liver abscess; failure to respond to metronidazole after 4-day treatment duration; empyema after amebic liver abscess rupture; large left-sided amebic liver abscess representing risk of rupture in the pericardium; and severely ill patient with imminent amebic liver abscess rupture. Surgical drainage of uncomplicated amebic liver abscess is generally unnecessary and should be avoided. Percutaneous catheter drainage improves the outcome in the treatment of amebic empyema and is life-saving in amebic pericarditis. Percutaneous catheter drainage should be used judiciously in the setting of localized intraabdominal fluid collections. Although controversial, it might be used to aspirate

large amebic liver abscesses (>300 cm

3

).

Medication Summary

Asymptomatic amebiasis should be treated with a luminal agent (iodoquinol,

paromomycin, diloxanide furoate) to eradicate infection. This recommendation is based on two arguments: First, invasive disease may develop; second, shedding of E histolytica cysts in the environment is a public health concern. Asymptomatic E dispar infections should not be treated, but education should be

pursued since it is a marker of fecal-oral contamination. Amebic colitis is first treated with a nitroimidazole derivative (metronidazole being the

only one available in the United States), followed by a luminal agent to eradicate colonization. Amebic liver abscess can be cured without drainage and even by one dose of

metronidazole. Clinical defervescence should occur during the first 3-4 days of treatment. Metronidazole failure may be an indication for surgical intervention. Treatment with a luminal agent should also follow. Disseminated amebiasis should be treated with metronidazole, which can cross the

brain-blood barrier. Empirical antibacterial agents should be used concomitantly if perforated viscus is a concern.

Amebicides

Class Summary

Parasite biochemical pathways are sufficiently different from the human host to allow

selective interference by chemotherapeutic agents in relatively small doses.

Iodoquinol (Yodoxin) Amebicidal against E histolytica. Considered effective against trophozoite and cyst forms.

Amebicidal and antibacterial aminoglycoside obtained from a strain of Streptomyces rimosus, active in intestinal amebiasis against trophozoite and cyst forms of E histolytica. Recommended for the treatment of Diphyllobothrium latum, Taenia saginata, Taenia solium, Dipylidium caninum, and Hymenolepis nana.

Diloxanide (Entamide, Furamide) Dichloroacetamide derivative. Amebicidal against trophozoite and cyst forms of E histolytica.

Active against various anaerobic bacteria and protozoa. Appears to be absorbed into cells. Intermediate metabolized compounds are formed and bind DNA and inhibit protein synthesis, causing cell death. Antimicrobial effect may be due to production of free radicals. Indicated for invasive amebiasis.

5-Nitroimidazole derivative used for susceptible protozoal infections. Indicated to treat intestinal amebiasis and amebic liver abscess caused by E histolytica in adults and children aged 3 y and older.